Elderly Breast Cancer Population Research Articles

Impact of 21-Gene Recurrence Score in an elderly breast cancer population before and after TAILORx

Impact of 21-Gene Recurrence Score in an elderly breast cancer population before and after TAILORx

Increasing Mortality in Korean Patients With Breast Cancer: High Mortality Rate in Elderly Breast Cancer Population Due to Suboptimal Treatment and Other Diseases.

BackgroundThe incidence of breast cancer in Asia, including Korea, has rapidly increased. Each country has shown different clinical features. This study presents a comprehensive understanding of breast cancer in different age groups in Korea and determines potential measures for improving patient survival.MethodsPatients diagnosed with invasive breast cancer stages I to III with available clinicopathologic and follow-up data were included in the study. Kaplan–Meier survival graphs were generated for each group and compared using log-rank test. The hazard ratio for each risk factor was calculated using the Cox regression model and the 95% confidence interval.ResultsThe final cohort included 833 patients with a mean age of 51.3±11.3 years (range, 22–89 years), and 191 (22.9%) of them were aged >60 years. Patients aged ≥60 years had worse overall survival (OS) and distant disease-free survival than those aged <60 years. Although no difference was observed in the tumor biology, elderly patients showed significant differences in practice patterns: they tended to undergo mastectomy (40.2% vs 62.8%, P<0.001), did not receive the standard chemotherapy (88.4% vs 69.3%, P < 0.001), and had a higher risk of developing second primary cancer or diseases other than breast cancer (1.2% vs 6.8%, P < 0.001), which significantly correlated with poor survival in elderly patients.ConclusionLess-than-the-standard treatment of care or development of a second primary disease resulted in poor prognosis in elderly patients in Korea. A multi-institutional and multinational study is warranted to elucidate the clinical features of breast cancer in Asian patients.

Quality of life for elderly breast cancer patients: a new regard.

The elderly are considered less tolerant to cancer management, most oncologists are not optimistic about clinical outcome and toxicity profile following of elderly cancer patients’ treatment. The use of the quality of life assessment may base the decision to treat breast cancer patients on more factors than just their ‘age’ alone. Our aim in this review is to address the quality-of-life (QoL) assessment importance on elderly breast cancer population who are treated with anticancer modalities.

Factors Associated with Functional Decline in Elderly Female Breast Cancer Patients in Appalachia.

BackgroundFunctional status has been previously shown in the elderly cancer population to predict both mortality as well as treatment tolerance. The goal of this study was to determine if there are certain subsets of the elderly breast cancer population that are at higher risk of experiencing functional decline following treatment.MethodsPatient charts from the Edwards Comprehensive Cancer Center in Huntington, West Virginia, from January 2006 – January 2016 were reviewed. Relevant inclusion criteria included patients of 65 years of age and older with a new diagnosis of Stage 0-III breast cancer. Functional decline was defined as an increase of at least one point in Eastern Cooperative Oncology Group (ECOG) scores within one year of diagnosis. ECOG performance status was subjectively determined by the physician. Fisher’s exact test and Pearson’s Chi-squared test were initially utilized to assess potential factors associated with functional decline such as pretreatment ECOG score, age at diagnosis, stage, hormone receptor status, type of surgery received, whether radiation therapy, chemotherapy, or hormonal therapy was received, medical comorbidities, body mass index (BMI), complaints of weakness at diagnosis, and ambulatory status. Factors that were found to be significant were further assessed via multivariate logistic regressions.ResultsThree-hundred and fourteen patients were identified as meeting inclusion criteria. At one-year follow-up, 45 patients (14.3% of the cohort) had documented functional decline. On initial analysis, factors associated with functional decline included Stage III disease (p=0.002) and complaints of weakness at diagnosis (p=0.004). Following multivariate analysis, Stage III disease (p = 0.02), complaints of weakness at diagnosis (p = 0.04), and bilateral mastectomy (p = 0.03) were significantly associated with functional decline.ConclusionPatients who were diagnosed with Stage III breast cancer, had complaints of weakness at time of diagnosis, or had bilateral mastectomies were more likely to have a decline in functional status at one-year follow-up. Awareness of factors associated with functional decline in the elderly Appalachian population with Stage 0-III breast cancer will be useful during discussions regarding patient expectations, treatment, and goals of care. Elderly breast cancer patients for whom bilateral prophylactic mastectomies are not indicated may be better served by lumpectomy alone (based on patient age, hormone receptor status, and tumor size), lumpectomy followed by radiation therapy, or unilateral mastectomy to maximize the likelihood of functional preservation following treatment.

Prognostic impact of breast cancer subtypes in elderly patients.

We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65–74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75–84 years among the old–old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %); p < 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %); p = 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2–11.4; p < 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9–6.4; p < 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease—not TNBC—featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted.

Abstract P2-08-17: Prognostic impact of breast cancer subtypes in elderly patients

Abstract Background We aimed to analyze the impact of BC subtypes on the clinical course with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly breast cancer population. Patients and Methods 571 patients ≥65 years receiving treatment for BC from 2007-2011 were identified from a BC database. BC subtypes and clinical characteristics including overall survival (OS) were obtained by chart review. Statistical analysis was performed using the Chi Square test, the log rank test and time depended covariate cox regression model as appropriate. Results Three-hundred-eighty/571 (63%) were grouped among the young-old (65-74 years), 182/571 (31.9%) among the old-old (75-84 years), and 29/571 (5,1%) among the oldest-old (≥85 years). 392/571 (68.8%) patients presented with luminal BC, 119/571 (20.8%) with HER2 positive and 59/571 (10.3%) with triple negative BC. After a median follow up of 38 months (range 0-204), 115/571 (20.1%) patients presented with metastatic recurrence. Highest recurrence rate was observed in HER2 positive BC patients (43/119 (36.1%)), followed by triple negative (15/59 (25.4%) and luminal BC (57/392 (14.5%); p&amp;lt;0.001; Chi Square test). BM occurred significantly more frequently in HER2 positive BC patients (9/119 (7.6%) compared to triple negative (2/59 (3.4%) and luminal BC patients (6/392 (1.5%); p=0.003; Chi Square test). Occurrence of metastases (HR 7.7; 95% CI 5.2-11.4; p&amp;lt;0.001) as well as development of BM (HR 3.5; 95% CI 1.9-6.4; p&amp;lt;0.001) had a significant impact on OS prognosis as entered in a time depended covariate cox regression model. Conclusions In contrast to younger BC patients, HER2 positive BC subtype and not triple negative BC subtype was linked to the most aggressive clinical course including the development of metastatic disease and BM in our elderly cohort. Citation Format: Bergen ES, Tichy C, Berghoff AS, Rudas M, Dubsky P, Bago-Horvath Z, Mader RM, Gnant M, Dieckmann K, Zielinski CC, Steger GG, Preusser M, Bartsch R. Prognostic impact of breast cancer subtypes in elderly patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-17.

Breast Cancer in the Elderly: Is MRI Helpful?

Appropriate use of magnetic resonance imaging (MRI) in elderly breast cancer (BC) patients remains unclear; we sought to identify the indications and implications of MRI use in our elderly BC population. Women 70 years of age or older at first BC diagnosis with an MRI performed at our institution either perioperatively or in follow-up were included from a prospectively maintained database from 2000 to 2010. Univariate logistic regression was used to test associations with disease identified by MRI only (additional ipsilateral, contralateral, or new cancer) following perioperative MRI. 305 BCs were imaged in 286 patients. 133 were imaged with MRI in the perioperative setting alone, 88 had only follow-up MRIs after BC treatment, and 65 had both. Indications for perioperative MRI include: extent of disease evaluation (181; 91%); occult primary (10; 5%); high-risk screening (5; 3%); and abnormal physical exam with negative conventional imaging (2; 1%). Disease identified by MRI only for occult primary cases was 4/10 (40%; 95% confidence interval: 12.2-73.8%) and 14/181 (7.7%; 95% confidence interval: 4.3-12.6%) for perioperative MRIs performed for extent of disease evaluation. Analysis of imaging and tumor characteristics failed to find significant predictors of disease identified by MRI only. A total of 369 post-treatment follow-up MRIs were performed in 148 patients with a median of 2 MRIs per patient (range 1-8), with seven cases of disease identified by MRI only (1.9%; 95% confidence interval: 0.8-3.9%). MRI had the greatest benefit in women presenting with an occult primary cancer and minimal additional benefit in elderly patients with BC undergoing MRI imaging for extent of disease evaluation or in post-treatment surveillance.

Abstract OT3-3-02: ASTER 70s UNICANCER phase III trial: Can a genomic prognosticator help tailoring adjuvant systemic treatment for luminal breast carcinoma in elderly women?

Abstract The benefit of adjuvant chemotherapy (CT) added to hormonal therapy (HT) compared with HT alone remains debated for women &amp;gt;70 with ER+ HER2- breast cancer (BC). Selection of valid indications might be improved by the use of better prognosticator. This trial compares the impact of both strategies on overall survival (OS) according to Genomic Grade (GG). Following surgery, ∼2,000 patients (Pts) will have a GG performed centrally on FFPE specimens by RT-PCR. Those with a high risk (high or equivocal GG) will be randomized to HT alone vs CT+HT. Pts with a low GG will be followed as an observational cohort. OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, willingness and health-related quality of life including specific ELD15. Translational research will focus on prognostic biomarkers and pharmacogenetics. Statistical design: sample size based on 4-year OS benefit favouring CT (87.5 vs 80%; HR 0.60); bilateral test α=0.05, β=0.20; 129 events expected in 700 randomized Pts enrolled over 4 years. From 04/12-05/14, 67 centres in France and Belgium have included 990 Pts aged 70-92. Only 31 GG evaluations were not performed (tumour blocks not available, 14; consent withdrawal or central pathology review discordance, 7 each; treatment choice, 3). In the main recruiting site, the study was not proposed to 20% of pre-screened Pts mostly because of team choice (50%) and inclusion criteria (25%). Amongst those informed, 66% accepted to participate. Median time to get GG information was 17 days (11-25) from sending tumour sample to providing the information to patient. Of 932 cases with GG report, 374 (40%), 187 (20%) and 362 (39%) were low, equivocal and high GG respectively; 9 tests (1%) failed for technical reasons. The proportion of high-risk tumours (high/equivocal GG 59%) is similar to that observed in general BC populations (40% to 60%) and only 21 of high-risk cases were not randomized (consent withdrawal, 6; treatment choice, 5; laboratory values, 4; tumour phenotype not confirmed or distant metastasis, 3 each). With 75% of target recruitment in &amp;lt; 2 years, we confirm the feasibility of such innovative multicentre program in an usually underserved population. This might help to better select adjuvant strategy in the elderly BC population and to avoid jeopardising any benefit if stymied by uncontrolled side effects. Citation Format: Coraline Dubot, Emmanuelle Bourbouloux, Olivier Mir, Sylvie Kirscher, Olivier Rigal, Jean-Marc Ferrero, Herve Cure, Emmanuel Blot, Djelila Allouache, Paul Cottu, Gilles Romieu, Claudia Lefeuvre, Emmanuelle Malaurie, Nicole Tubiana-Mathieu, Magali Lacroix-Triki, Florence Rollot, Hélène Peyro-Saint-Paul, Christine Orsini, Franck Bonnetain, Etienne Brain. ASTER 70s UNICANCER phase III trial: Can a genomic prognosticator help tailoring adjuvant systemic treatment for luminal breast carcinoma in elderly women? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-3-02.

330TiP - Aster 70S Unicancer Phase III Trial : Adjuvant Treatment for Women Over 70 with Luminal Breast Cancer

ABSTRACT Background: Benefit of the additional adjuvant chemotherapy (CT) compared with hormonal therapy alone (HT) remains debated for women >70 with ER+ HER2- breast cancer (BC) and aggressive characteristics. This trial compares the impact of both strategies on overall survival (OS). Trial design: Following surgery, ∼2,000 patients (Pts) will have a Genomic Grade (GG) performed centrally on FFPE specimens by RT-PCR. Those with a high risk defined as high or equivocal GG will be randomized to HT alone vs CT + HT. Pts with a low GG will be followed as an observational cohort. OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, willingness and health-related quality of life including specific ELD15. Translational research will focus on prognostic biomarkers and pharmacogenetics. Sample size based on an expected 4-year OS benefit (87.5 vs 80%; HR 0.60), with bilateral test a = 0.05 and a statistical power of 80%. It will require to observe 129 events and to randomize 700 Pts over a planned duration of 4 years. As of March 2014, 65 centres in France and Belgium have included 890 Pts aged 70-92. Only 30 GG evaluations were not performed (consent withdrawal, 7; tumour blocks not available, 14; central pathology review discordance, 6; treatment choice, 3). In the main participating site, the study was not proposed to 20% of pre-screened Pts mostly because of team choice (50%) and inclusion criteria (25%). Amongst those informed, 66% accepted to participate.). Overall, of 860 cases with GG report, 346 (41%), 167 (19%) and 338 (39%) were low, equivocal and high GG respectively; 9 tests (1%) failed for technical reasons. The proportion of high risk tumours (high + equivocal GG, 59%) is similar to those observed in general BC populations (40% to 60%) and only 19 of high-risk cases were not randomized (consent withdrawal, 6, distant metastases, 3, treatment choice, 5, tumour phenotype not confirmed, 3, or laboratory values, 2). With 69% of target recruitment at mid-term of the planned inclusion period, we confirm the feasibility of such a multicentre program investigating the role of an innovative prognostic signature to better select adjuvant strategy in the elderly BC population. Disclosure: H. Peyro Saint Paul: employee and stock holder QIAGEN. All other authors have declared no conflicts of interest.

Inferring breast cancer concomitant diagnosis and comorbidities from the Nationwide Inpatient Sample using social network analysis

Breast cancer is a complex disease and may be accompanied by other multiple health conditions. The present study investigates associations between diagnosis codes in breast cancer patients using the Nationwide Inpatient Sample data. Concomitant diagnoses codes are identified by statistically significant associations between the diagnoses codes in a given breast cancer patient. These are subsequently represented in the form of a network (Breast Cancer Concomitant Diagnosis Network (BCCDN)). In contrast to more classical approaches, BCCDN provides system-level insights and convenient visualization reflected by the complex wiring patterns between the diagnoses codes. Social network analysis is used to investigate highly connected codes in the BCCDN network, and their variation across three different populations: (i) the deceased breast cancer population (ii) the elderly breast cancer population (age>65 years) and (iii) the adult breast cancer population (age <=65 years). BCCDNs were investigated across years 2005 and 2006 in order to identify associations that are robust to the stratified sampling and population heterogeneity as well as possible errors in documentation characteristic of observational healthcare data. The results presented validate known chronic comorbidities and their persistence across the deceased and elderly breast cancer population. They also provide novel associations and potential comorbidities in breast cancer patients that may warrant a more detailed investigation.

Abstract OT3-1-10: ASTER 70s (UNICANCER phase III trial): Is personalized adjuvant treatment for women over 70 with luminal breast cancer the way to go?

Abstract Background The question of the additional benefit of adjuvant chemotherapy (CT) compared to hormonal therapy alone (HT) for women &amp;gt;70 with ER+ / HER2- breast cancer (BC) and aggressive characteristics is still unsolved. This trial compares the impact of both strategies on overall survival (OS). Trial design Following surgery, ∼2,000 patients will have a Genomic Grade (GG) centrally performed on FFPE specimens. Those with a high or equivocal GG will be randomized HT alone vs HT+CT. Patients with low GG will be followed as an observational cohort. The study, on-going in France since April 2012, has been recently activated in Belgium. Eligibility criteria Any ER+ HER2- BC after complete surgery, M0, any pT or pN. Normal organ functions. No specific BC treatment before surgery. Contralateral BC, invasive BC after ductal carcinoma in situ and isolated local invasive relapse when adjuvant systemic treatment is considered are all eligible. Multifocal or bilateral are eligible according to focus with worst GG. The G8 screening tool is used as stratification criteria for randomization. Specific aims OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, acceptability/willingness and health-related quality of life including specific ELD15. The Lee's 4-year mortality score is calculated. Translational research will focus on prognostic biomarkers and pharmacogenetic, investigating also the impact of treatments on putative ageing biomarkers as CRAMP, stathmin, EF-1α and chitinase and telomeres length. Statistical methods Sample size based on 4-year OS (87.5 vs 80%), bilateral test, α = 0.05, β = 0.20 and HR = 0.60. In total, 129 events are expected, requiring 340 patients/arm. Considering those lost to follow-up, ∼700 patients in total should be included (5 extra patients/year). Present accrual and target accrual As of May 2013, 43 centres have included 406 Patients aged 70-88. Only 14 GG evaluations were not performed for the following reasons: Patients consent withdrawal (n = 3), tumour block not available for the GG test (n = 5), CT not a treatment option anymore (patients or investigator's decision) (n = 2) or tumour status (ER+/HER2-) not confirmed by central review (n = 4). 8 GG evaluations are on-going. Of 384 cases with GG report, 160 (42%), 151 (39%) and 65 (17%) were respectively GG-1 (low risk), GG-3 (high risk) and GG-EQ (equivocal); 8 (2%) tests failed for technical reasons. The proportion of high GG in the study (53%) is similar to those observed in previous studies in general BC populations (40% to 60%). Of 216 GG-3/-EQ cases, 4 were not randomized because of distant metastases detected during extensive work-up (n = 3) and Patient refusal of CT treatment before randomization (n = 1). Five randomizations are on-going. GG determination was obtained in 384 leading to randomization in 207, totalizing so far 30% of the projected recruitment for the primary objective. This confirms the feasibility of such multicentre strategic program with an innovative prognostic signature in the elderly BC population. Contact information c-orsini@unicancer.fr. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-10.

Abstract P2-02-06: Breast cancer in the elderly: Is MRI helpful?

Abstract Background: Guidelines support screening MRI in select high-risk groups; however, MRI is frequently obtained perioperatively and for breast cancer (BC) follow-up. Appropriate use of MRI in elderly patients remains unclear; we sought to identify the indications and implications of MRI use in our elderly BC population. Methods: Women 70 years of age or older at first BC diagnosis with an MRI performed at our institution either perioperatively or in follow-up were included from a prospectively maintained database from 2000-2010. Univariate logistic regression was used to test associations with upgrade (additional ipsilateral, contralateral, new cancer, or recurrence) following perioperative MRI. Kaplan-Meier and competing risks methods were used to estimate survival and cumulative incidence. Results: 305 breast cancers were identified in 286 patients. 133 patients were imaged with an MRI in the perioperative setting alone, 88 had only follow-up MRIs after BC treatment, and 65 had both. Patient, tumor, and treatment data are summarized in Table 1. TableFactorN = 305Age, yearsMedian: 73 (range, 70-90)Means of Diagnosis Imaging189 (62%)Physical abnormality109 (36%)Other/incidental7 (2%)Mammographic density* Fatty21 (7%)Mild96 (32%)Moderate166 (55%)Extreme18 (6%)Tumor size*Median: 1.2cm (range 0.1-7.0)Histology DCIS +/- microinvasion44 (14%)Invasive ductal181 (59%)Invasive lobular68 (22%)Other12 (4%)ER positive*225 (86%)PR positive*159 (61%)HER2/neu positive*17 (7%)Final surgery* Lumpectomy217 (71%)Mastectomy87 (29%)Radiation following lumpectomy*169 (80%)Adjuvant chemotherapy*81 (27%)Adjuvant endocrine therapy*200 (69%)*for patients with information available Indications for perioperative MRI include: extent of disease evaluation for known cancer (155;78%); abnormal imaging (13;7%); protocol (13;7%); occult primary (10;5%); high-risk screening (5;3%); and abnormal physical exam (2;1%). MRI upgrade for occult primary cases was 4/10 (40%; 95% confidence interval (CI), 12.2-73.8%) and 21/188 (11.2%; 95% CI, 7.1-16.6%) for the remainder of perioperative cases; comprised of 9 contralateral and 5 additional ipsilateral cancers in women undergoing MRI for extent of disease evaluation, and 7 new cancers identified on MRIs for high-risk screening or abnormal imaging/physical exam. These lesions consisted of 10 DCIS and 11 node-negative invasive cancers (median size, 7mm; range, &amp;lt;1-18mm). Analysis of imaging and tumor characteristics failed to find significant predictors of upgrade. 369 postoperative follow-up MRIs were performed in 153 patients with a median of 2 MRIs per patient (range, 1-8), and identified 7 upgrades (1.9%; 95% CI, 0.8-3.9%), for an overall patient upgrade rate of 4.6% (7/153). Median follow-up was 5.3 years. Five-year incidence of local, regional, and distant recurrence, and contralateral BC was 3.3%, 1.3%, 4%, and 3.7%, respectively. Five-year overall and recurrence-free survival (RFS) was 92% and 85.7%, respectively. Conclusion: Our elderly patients had an excellent overall and RFS. MRI had the greatest benefit in women presenting with an occult primary. 11% of perioperative MRIs identified additional or new disease, while only 2% of follow-up MRIs resulted in an upgrade, calling into question the benefit of follow-up MRI imaging in elderly BC patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-02-06.

The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population

Background: Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. Patients and Methods: Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). Results: Among 59 patients identified, 51 patients were evaluable (median age 76 years). The rate of any adverse event was 20% (10/51). The most relevant cardiac adverse event consisted of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other toxicities included moderate hypersensitivity reactions during trastuzumab infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and concurrent chemotherapy were associated with a higher incidence of toxic events. Previous radiotherapy, concurrent endocrine therapy and different trastuzumab-based regimens did not seem to influence toxicity. Conclusions: Our data suggest that trastuzumab has a good safety profile in nonfrail women aged 70 years and older. These favorable findings may be related to a limited number of anthracycline pretreatments, patient selection and a close cardiologic monitoring.

32P Ageing Biomarkers in an Elderly Breast Cancer Population: Correlation with Comprehensive Geriatric Assessment (CGA)

ABSTRACT Introduction With increasing life expectancy in the western population, the field of geriatric oncology has been expanding rapidly over the last years. The concept that treatment of cancer in the older person is possible, and can be beneficial even at high age, has been confirmed. However, potential benefit of treatment must be balanced against risks of toxicity and decline in functionality and quality of life. This balance is influenced by the patient’s biological age and life expectancy. CGA can reflect biological age to a certain extent, but with potential limitations in terms of validity, sensitivity and reliability. Better ageing markers are therefore needed, to refine selection of patients for therapy. Methods We retrospectively analyzed a panel of potential ageing biomarkers in blood samples collected at diagnosis from 162 breast cancer patients (≥70 years of age) for whom CGA at the same time point was also available. Patients were divided into 3 categories (Fit-Vulnerable-Frail) on the basis of CGA, using Balducci’s definition. Analyzed biomarkers were circulating levels of IL-6, MCP-1 (CCL2), RANTES (CCL5) and mean leukocyte telomere length. The first three markers were determined by ELISA on serum/plasma, telomere length was determined by RT-PCR on leukocyte DNA. Results Mean levels of circulating IL-6 correlated with levels of frailty (Mean for Fit: 4,40 pg/mL, SEM 1.96 versus Mean for Frail 7.02, SEM 1.77; p = 0.018). Mean telomere length decreased with increasing frailty, although not statistically significant (Mean T/S ratio for Fit: 1.15, SEM 0.14 versus Mean T/S ratio for Frail: 0.92, SEM 0.05; p = 0.99). No correlation between frailty and mean circulating levels of MCP-1 or RANTES could be demonstrated. Conclusion Plasma levels of circulating IL-6 are correlated significantly with the level of frailty determined by CGA in older breast cancer patients. We also saw a decrease of telomere length with increasing frailty, although not statistically significant. IL-6 and telomere length mandate further investigation as markers of biological age in cancer patients, and also as predictors for treatment toxicity and outcome, in order to improve appropriate treatment selection. Disclosure All authors have declared no conflicts of interest.

Age-Specific Nonpersistence of Endocrine Therapy in Postmenopausal Patients Diagnosed with Hormone Receptor–Positive Breast Cancer: A TEAM Study Analysis

Early discontinuation of adjuvant endocrine therapy may affect the outcome of treatment in breast cancer patients. The aim of this study was to assess age-specific persistence and age-specific survival outcome based on persistence status. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational trial were included. Nonpersistence was defined as discontinuing the assigned endocrine treatment within 1 year of follow-up because of adverse events, intercurrent illness, patient refusal, or other reasons. Endpoints were the breast cancer-specific and overall survival times. Analyses were stratified by age at diagnosis (<65 years, 65-74 years, ≥75 years). Overall, 3,142 postmenopausal breast cancer patients were included: 1,682 were aged <65 years, 951 were aged 65-74 years, and 509 were aged ≥75 years. Older age was associated with a higher proportion of nonpersistence within 1 year of follow-up. In patients aged <65 years, nonpersistent patients had lower breast cancer-specific and overall survival probabilities. In patients aged 65-74 years and patients aged ≥75 years, the survival times of persistent and nonpersistent patients were similar. Nonpersistence within 1 year of follow-up was associated with lower breast cancer-specific and overall survival probabilities in patients aged <65 years, but it was not associated with survival outcomes in patients aged 65-74 years or in patients aged ≥75 years. These results suggest that extrapolation of outcomes from a young to an elderly breast cancer population may be insufficient and urge age-specific breast cancer studies.

Clinical epidemiology of breast cancer in the elderly

Breast cancer will increasingly become a disease affecting the lives of older women, especially in more developed countries, the prevalence rising up to 7% over age 70 in the near future. A review of the population-based literature and an analysis of the data of the Eindhoven Cancer Registry and European data regarding the diagnosis, treatment and prognosis showed that the proportion with unstaged and advanced disease (stages III and IV) is higher among elderly patients compared to younger ones and that their treatment is generally less aggressive, although the proportion receiving chemotherapy is increasing since the early 1990s. Disease specific (or relative) survival of elderly breast cancer patients is generally lower and the prevalence of serious (life expectancy affecting) co-morbidity is higher (>50% in patients over age 70). Because of large individual variations in physical and mental conditions, limited evidence from RCTs and personal preferences prevailing in the decision-making process, treatment of older breast cancer patients seems difficult to fit into guidelines. Therefore, alternative research strategies are needed to understand and improve the care for the elderly breast cancer population, such as descriptive (registry-based) studies and a qualitative, individual-based approach.

Reproductive risk factors of breast cancer in elderly population. A single centre study

21187 Background: Relationship between reproductive variables and cancer risk has been yet established. Protective effect of late age at menarche (≥ 11) and high parity (≥ 4) and the increased risk of nulliparous women, older age at first birth (AFB) (≥ 28) and older age at menopause (≥ 52) seems to act differently in pre vs. postmenopausal elderly women. The aim of this study was to describe recognized reproductive risk factors for breast cancer in a selected population of a single centre. Methods: A cross- sectional study of women diagnosed ≥ 70 years. We selected women with removed early breast cancer and on follow-up. No disease recurrences were allowed. Between January 2005 to June 2006. Described reproductive risk factors for breast cancer were collected. Tumour characteristics also. Results: 91 patients were recruited. Mean age at time of diagnosis: 76 (70–92); mean age at study 80 (71- 95). Reproductive factors: late age at menarche (12; 9–16; percentile 75: 14) and late age at menopause: 48 (29–56); 75% ≥ 52 years old were common. Nulliparous women were similar at described in other series (10%); parity 2 (0–9); percentile 75: 3;late AFB: 26 (19–40); percentile 75: 29 years. No one had taken hormonal treatment. Only 16% had familiar history of breast cancer and 9% personal history. Almost all (84%) had positive tumours for the oestrogen receptor and 76% for progesterone receptor. 91% had ductal histology and 54% had II stage. Conclusions: Discussion: unexpected associations between classical reproductive risk factors and breast cancer on elderly patients have been described in other series. It seems that late age at menarche and late age at menopause is common in elderly breast cancer population, as in our serie. Nulliparous elderly continue to have risk but seems that the protective effect of parity dissipated in these population. Older age at first birth (≥28) is consistently associated with increased breast cancer risk. Conclusion: our study is based on a high selected population and clearly has a selection bias. Our results cannot be generalized to other populations but describes our patients. The results therefore should be internally valid. And it seems to coincide with other studies. No significant financial relationships to disclose.

Pattern of presentation and treatment of early primary breast cancer in the elderly

11030 Background: There is a high prevalence of breast cancer in the elderly population; however the majority of data available is obtained from younger patients. This study aimed to identify the patterns of presentation and treatment subsequently received by elderly women with early breast cancer. Methods: Patients included were &gt;70 years and had operable primary breast cancer (&lt;5 cm) managed in a dedicated clinic. Personal characteristics, patterns of presentation, pathological features of diagnostic needle core biopsies and treatments both recommended and received were reviewed in 265 consecutive female patients diagnosed over a 30-month period (between January 2004 and June 2006). Results: The mean age was 78.5 (range: 70–100 years). Majority (83%) presented with symptomatic cancer with the remaining ones detected through mammographic screening. These cancers were predominantly oestrogen receptor positive (histochemical (H) score &gt;10) (84%) with high H scores (83% had H scores &gt;200). Most of them were grade 2 (63%), followed by grade 1 and 3. Treatment undertaken was often in compliance with the clinicians’ advice if specifically recommended; however, when choice was given, there was a tendency to accept non-operative intervention. Documented reasons include surgical refusal, feeling un-fit for surgery and personal commitments disallowing post-operative recovery time. In addition, patients who received primary hormone therapy were on average 7 years older and suffered significantly more co-morbidity than those who had surgery. Conclusions: The elderly breast cancer population often receive different treatments possibly due to biological characteristics and personal reasons distinct from their younger counterpart. Further work is ongoing to link these findings to long-term clinical outcome. [Table: see text] No significant financial relationships to disclose.

Formestane is feasible and effective in elderly breast cancer patients with comorbidity and disability.

Age is a major risk factor for solid tumors, including breast cancer. The majority of elderly breast cancer patients have oestrogen-dependent tumors, thus, tamoxifen is widely administered. However, it has been noted that tamoxifen-related thrombotic events are not exceptional. Due to the increasing prevalence of comorbidity, including vascular diseases, with age, such events are more frequently observed in the aged patients. Formestane, a selective steroidal aromatase inhibitor, may represent a therapeutic option after failure with tamoxifen, or in the presence of vascular diseases contraindicating its administration. The present report provides a new clinical experience on a consecutive series of 45 elderly breast cancer women affected by moderate to severe degree of comorbidity and disability measured by a Comprehensive Geriatric Assessment (CGA) scale validated on oncological patients. Formestane was given intramuscularly at the dose of 250 mg every 2 weeks. The study included 31 patients who had metastatic disease, and 14 who received formestane as an adjuvant treatment. Median age was 74 years (range 65-93), with nine patients > 80 years. Median ECOG Performance Status (PS) was one. The more frequent comorbidities observed in our series were arthrosis-arthritis (64.4% of patients), hypertension (44.4%), vascular diseases (35.5%), CNS diseases (28.8%). Twenty percent of patients presented at least one dependency in Activities of Daily Living (ADL) and 51.2% in Instrumental Activities of Daily Living (IADL). The treatment was well tolerated - only two patients interrupted formestane because of minor adverse reaction at the injection site and generalised itching. In particular Formestane was not responsible for any worsening of pre-treatment comorbidities, especially hypertension and vascular diseases. Objective responses (OR) were observed in 11.1% of advanced patients, while the disease was stabilised in 51.8% subjects. Median duration of OR was 12 months; median overall survival was 11 months. Among patients receiving formestane as adjuvant treatment, three relapsed, with a time to failure (TTF) of 12 months. Formestane is effective and minimally toxic in an elderly breast cancer population with comorbidities and disabilities measured by CGA.